Possible Application of Melatonin in Long COVID

Cardinali, Daniel P.; Brown, Gregory M.; Pandi-Perumal, Seithikurippu R.

doi:10.3390/biom12111646

Cited by 24 publications

(17 citation statements)

References 89 publications

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“…Melatonin plays multi-functional roles including the regulation of circadian rhythms, immune modulation, oxidative processes, apoptosis, and mitochondrial homeostasis 655 . Melatonin deficiency may lead to CVD with manifestations of hypertension and myocardial ischemia/reperfusion injury, which are prevalent in COVID-1; as well as neuro-cognitive complications such as brain fog, sleep disorders and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which are persistent among PASC 656 , 657 .…”

Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

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SARS‐CoV‐2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus–host protein–protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia (‘cytokine storm’), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25–70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new ‘onset’ clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.

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Section: Long-covid/pasc: Precision Nutrition To Reset Virus-induced ...mentioning

confidence: 99%

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Naidu,

Wang,

Rao

et al. 2024

npj Sci Food

View full text Add to dashboard Cite

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“…23 Evidence further shows signs of skeletal muscle weakness, wasting, and exercise intolerance, 22 rather than the sole presence of low grade inflammation, 24 along with poor neuroimmunity and oxidative processes. 25 While the world awaits more data and a possible model for reducing or preventing long COVID complications, a role for antioxidants such as melatonin, 24,26 plus supplements 27 such as Co enzyme Q delivery and/or spa therapy has been put forth. 28,29 However, clearly extensive individualized assessments and an ensuing array of treatment options based on the patient's personal profile appears imperative to avert what has been termed a pervasive and possible future case of widespread 'medical devastation'.…”

Section: Resultsmentioning

confidence: 99%

Aging and long COVID-19 syndrome: what’s new in 2023?

Marks¹

2023

MOJGG

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Since 2019 that saw the onset of the COVID-19 pandemic, its ongoing impact on many older adults remains a persistent public health concern, especially among those who report suffering from long or post-acute COVID-19 disease health challenges. This report presents data published largely since January 1 2023 on this topic and concerning: Long COVID or COVID-19, Older Adults, Post-Acute COVID-19 Outcomes, and Prevention. Data show that even though long COVID-19 was discussed in 2021 at some length, it still remains a relatively unchartered poorly understood topic in which a sizeable percentage of older adult COVID-19 survivors may experience delayed features of breathing, movement, cognitive and mental health challenges. What causes the observed and perceived problems, what may help to identify who is at risk, and what will reduce these remains unknown, but may benefit from insightful research and extended observations and possible.

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“…Furthermore, patients infected with SARS-CoV-2 may have prolonged symptoms of cognitive impairment, fatigue, and respiratory and metabolic system abnormalities for six months to two years following infection, implying long-COVID syndrome. Melatonin may have potential therapeutic benefits on myalgic encephalomyelitis and chronic fatigue syndrome, but this still needs further prospective study [ 173 ]. Overall, melatonin is a promising potential therapeutic agent for COVID-19 cases with mild to critical severity, but further prospective multicenter randomized control trials concerning age and comorbidities are needed.…”

Section: Melatonin and Covid-19mentioning

confidence: 99%

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

Yiang

et al. 2023

Viruses

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Aging processes, including immunosenescence, inflammation, inflammasome formation, genomic instability, telomeric attrition, and altered autophagy, are involved in viral infections and they may contribute to increased pathophysiological responses to the SARS-CoV-2 infection in the elderly; this poses additional risks of accelerated aging, which could be found even after recovery. Aging is associated with oxidative damage. Moreover, SARS-CoV-2 infections may increase the production of reactive oxygen species and such infections will disturb the Ca++ balance via an endoplasmic reticulum (ER) stress-mediated unfolded protein response. Although vaccine development and anti-inflammation therapy lower the severity of COVID-19, the prevalence and mortality rates are still alarming in some countries worldwide. In this review, we describe the involvement of viral proteins in activating ER stress transducers and their downstream signals and in inducing inflammation and inflammasome formation. Furthermore, we propose the potential of melatonin as an ER stress modulator, owing to its antioxidant, anti-inflammatory, and immunoregulatory effects in viral infections. Considering its strong safety profile, we suggest that additive melatonin supplementation in the elderly could be beneficial in treating COVID-19.

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Possible Application of Melatonin in Long COVID

Cited by 24 publications

References 89 publications

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID

Aging and long COVID-19 syndrome: what’s new in 2023?

Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment

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